Henry Kuttner was born in Los Angeles. His father was a bookseller who had lived in San Francisco since 1859. Kuttner grew up in relative poverty following his father's death. As a young man he worked for his uncle's literary agency before selling his first story, “The Graveyard Rats,” to Weird Tales in 1936. He was on the fringes of fandom, being a busy correspondent, and an occasional contributor to fanzines. He was part of the inspiration for the character Matt Duncan in Rocket to the Morgue.

Kuttner was known for his literary prose and worked in close collaboration with his wife, C. L. Moore. They met through their association with the “Lovecraft Circle,” a group of writers and fans who corresponded with H. P. Lovecraft. Lovecraft sent Kuttner a batch of his unpublished stories with a request to read them, then to forward them to Moore, who had been selling fiction for a decade and was another correspondent of Lovecraft's. She and Kuttner fell into correspondence over the matter and were married on June 7, 1940. Their work together spanned the 1940s and 1950s and most of the work was credited to pseudonyms, mainly Lewis Padgett and Lawrence O'Donnell. They also used the pseudonyms of Keith Hammond, Kelvin Kent, and Robert O. Kenyon, among several others.

His more famous books included the following SF and fantasy titles: A Gnome There Was (1950); Fury (1950); Tomorrow and Tomorrow & The Fairy Chessman (1951); Robots Have No Tails (1952); Well of the Worlds (1953); Ahead of Time (1953); Mutant (1953); Beyond Earth's Gates (1954); Bypass to Otherness (1961); Earth's Last Citadel (1964); Valley of the Flame (1964); The Time Axis (1965); The Dark World (1965); The Creature from Beyond Infinity (1968); and The Mask of Circe (1971). Several of these books were written in collaboration with his wife and published under their “Lewis Padgett” pen name. The Best of Henry Kuttner was issued by the Science Fiction Book Club in 1975. Kuttner also published several mysteries, usually written with his wife.

He received a Gernsback Award (short fiction) in 1983 for a story, “Vintage Season,” he wrote with Moore in 1946.

Kuttner spent the middle 1950s getting his master's degree before dying of a heart attack in Los Angeles in 1958 — one of the more prominent casualties of the Year of the Jackpot. He was well-liked — in an obituary, Theodore Sturgeon said of him, "I never heard a bad thing about Henry Kuttner. I never saw evil of any kind in him. I never knew I could miss so very much someone I had seen so seldom. He shouldn't have died."